Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000719
UniProt IDP43235
Primary gene name(s)CTSK
Synonym gene name(s)CTSO, CTSO2
Protein nameCathepsin K
Protein functionClosely involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Displays potent endoprotease activity against fibrinogen at acid pH. May play an important role in extracellular matrix degradation.
Subcellular locationLysosome.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P43235
Gene Ontology
(Biological Process)
Complete annatation
bone resorption [GO:0045453];
collagen catabolic process [GO:0030574];
extracellular matrix disassembly [GO:0022617];
intramembranous ossification [GO:0001957];
positive regulation of protein targeting to mitochondrion [GO:1903955];
proteolysis [GO:0006508];
proteolysis involved in cellular protein catabolic process [GO:0051603];
regulation of mitophagy [GO:1903146];
toll-like receptor signaling pathway [GO:0002224]
Gene Ontology
(Molecular Function)
Complete annatation
collagen binding [GO:0005518];
cysteine-type endopeptidase activity [GO:0004197];
cysteine-type peptidase activity [GO:0008234];
fibronectin binding [GO:0001968];
proteoglycan binding [GO:0043394];
serine-type endopeptidase activity [GO:0004252]
Gene Ontology
(Cellular Component)
Complete annatation
endolysosome lumen [GO:0036021];
extracellular region [GO:0005576];
extracellular space [GO:0005615];
lysosome [GO:0005764]
Protein-protein interaction107893
Phylogenetic treeP43235
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD3-1.524541585638171.72008353217512e-050.000100484879833114
AZA vs. DISU0.7821358159550610.01965107205401720.331713617180577
AZA vs. IL7-0.1301993729743610.5473830657877840.999311006273513
AZA vs. SAHA0.6107426422604280.01979274924014980.153396350666334
DISU vs. CD32.29120276177956.89547086096809e-091.11526102744885e-07
DISU vs. IL7-0.9170014539427120.005438916471672830.0789900441333987
DISU vs. SAHA-0.1669340102999360.6685189872957140.898933766732129
DMSO vs. AZA0.04993506143685930.7969682604036521
DMSO vs. CD31.558098991673966.730957395229e-064.03188362461729e-05
DMSO vs. DISU-0.7358838911470820.03051897439588310.351971296434249
DMSO vs. IL7-0.1713676925926920.3982561653936680.844797508240592
DMSO vs. SAHA0.5556259132691760.03608447979104020.207772596630552
HIV vs. Mock in Activation-0.5516528188865740.4113535430184870.999983755607037
HIV vs. Mock in Latency-0.09850390510300290.6855366168462690.999834320637052
IL7 vs. CD31.405228105314785.32960912120739e-050.000335981590480799
SAHA vs. CD32.110192389530063.86446024069897e-084.53562428561788e-07
SAHA vs. IL70.7385595355987940.004780094790325820.0371801593753206
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
0.5107 0.03183

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) TRUE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.482692 0.0196926
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
unknown unknown unknown unknown unknown
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB03405 1-[N[(Phenylmethoxy)Carbonyl]-L-Leucyl-4-[[N/N-[(Phenylmethoxy)Carbonyl]-/Nl-Leucyl]Amino]-3-Pyrrolidinone/N experimental unknown unknown
DB03642 Benzofuran-2-Carboxylic Acid {(S)-3-Methyl-1-[3-Oxo-1-(Pyridin-2-Ylsulfonyl)Azepan-4-Ylcarbamoyl]Butyl}Amide experimental unknown unknown
DB03891 1,5-Bis(N-Benzyloxycarbonyl-L-Leucinyl)Carbohydrazide experimental unknown unknown
DB04244 1-[2-(3-Biphenyl)-4-Methylvaleryl)]Amino-3-(2-Pyridylsulfonyl)Amino-2-Propanone experimental unknown unknown
DB05736 MIV-701 investigational unknown unknown
DB07563 1-{7-cyclohexyl-6-[4-(4-methylpiperazin-1-yl)benzyl]-7H-pyrrolo[2,3-d]pyrimidin-2-yl}methanamine experimental unknown unknown
DB07592 (1R)-2-METHYL-1-(PHENYLMETHYL)PROPYL[(1S)-1-FORMYLPENTYL]CARBAMATE experimental unknown unknown
DB07593 1-(PHENYLMETHYL)CYCLOPENTYL[(1S)-1-FORMYLPENTYL]CARBAMATE experimental unknown unknown
DB01858 [1-(4-Fluorobenzyl)Cyclobutyl]Methyl (1s)-1-[Oxo(1h-Pyrazol-5-Ylamino)Acetyl]Pentylcarbamate experimental unknown unknown
DB07965 6-(cyclohexylamino)-9-[2-(4-methylpiperazin-1-yl)-ethyl]-9H-purine-2-carbonitrile experimental unknown unknown
DB04234 N2-({[(4-Bromophenyl)Methyl]Oxy}Carbonyl)-N1-[(1s)-1-Formylpentyl]-L-Leucinamide experimental unknown unknown
DB03456 N2-[(benzyloxy)carbonyl]-n1-[(3S)-1-cyanopyrrolidin-3-yl]-l-leucinamide experimental unknown unknown
DB02869 3-amino-5-phenylpentane experimental unknown unknown
DB08270 N-(2-AMINOETHYL)-N~2~-{(1S)-1-[4&,39;-(AMINOSULFONYL)BIPHENYL-4-YL]-2,2,2-TRIFLUOROETHYL}-L-LEUCINAMIDE experimental unknown unknown
DB08594 TERT-BUTYL 2-CYANO-2-METHYLHYDRAZINECARBOXYLATE experimental unknown unknown
DB04523 Tert-Butyl(1s)-1-Cyclohexyl-2-Oxoethylcarbamate experimental unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1ATK X-ray 2.2Å A=115-329.
1AU0 X-ray 2.6Å A=115-329.
1AU2 X-ray 2.6Å A=115-329.
1AU3 X-ray 2.5Å A=115-329.
1AU4 X-ray 2.3Å A=115-329.
1AYU X-ray 2.2Å A=115-329.
1AYV X-ray 2.3Å A=115-329.
1AYW X-ray 2.4Å A=115-329.
1BGO X-ray 2.3Å A=115-329.
1BY8 X-ray 2.6Å A=16-329.
1MEM X-ray 1.8Å A=115-329.
1NL6 X-ray 2.8Å A/B=115-329.
1NLJ X-ray 2.4Å A/B=115-329.
1Q6K X-ray 2.1Å A=115-329.
1SNK X-ray 2.4Å A=116-329.
1TU6 X-ray 1.7Å A/B=115-329.
1U9V X-ray 2.2Å A=113-329.
1U9W X-ray 2.3Å A=113-329.
1U9X X-ray 2.1Å A=113-329.
1VSN X-ray 2.0Å A=115-329.
1YK7 X-ray 2.5Å A=115-329.
1YK8 X-ray 2.6Å A=115-329.
1YT7 X-ray 2.3Å A=115-329.
2ATO X-ray 2.0Å A=115-329.
2AUX X-ray 2.4Å A=115-329.
2AUZ X-ray 2.3Å A=115-329.
2BDL X-ray 2.0Å A=115-329.
2R6N X-ray 1.9Å A=113-329.
3C9E X-ray 1.8Å A=115-329.
3H7D X-ray 2.2Å A/E=115-329.
3KW9 X-ray 1.8Å A=115-329.
3KWB X-ray 2.0Å X/Y=115-329.
3KWZ X-ray 1.4Å A=115-329.
3KX1 X-ray 1.5Å A=115-329.
3O0U X-ray 1.8Å A=115-329.
3O1G X-ray 1.6Å A=115-329.
3OVZ X-ray 2.0Å A=121-329.
4DMX X-ray 1.7Å A=115-329.
4DMY X-ray 1.6Å A/B=115-329.
4N79 X-ray 2.6Å A=115-329.
4N8W X-ray 2.0Å A=115-329.
4X6H X-ray 1.0Å A=115-329.
4X6I X-ray 1.8Å A=115-329.
4X6J X-ray 1.5Å A=115-329.
4YV8 X-ray 2.0Å A=115-329.
4YVA X-ray 1.8Å A=115-329.
5J94 X-ray 2.6Å A=107-329.
7PCK X-ray 3.2Å A/B/C/D=16-329.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Tat upregulates 20869948

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04142 Lysosome - Homo sapiens (human)
hsa04210 Apoptosis - Homo sapiens (human)
hsa04380 Osteoclast differentiation - Homo sapiens (human)
hsa04620 Toll-like receptor signaling pathway - Homo sapiens (human)
hsa05323 Rheumatoid arthritis - Homo sapiens (human)